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Pyelonephritiso Ascending urinary tract infection

Reaches Pyelum of kidneyo Dividing into: A) Acute Pyelonephritis B) Chronic Pyelonephritis

Acute pyelonephritis (APN) Epidemiology:

i. More common in women than meno Women have a short urethra

Risk Factors:i. Urinary Tract Obstruction

ii. Medularry Sponge kidneyiii. Diabetes mellitusiv. Preganancyv. Sickle cell trait/disease

Pathogenesis:i. Vesicoureteral reflux (VUR) with ascending infection

o Intravesical portion of the ureter is normally

compressed with micturition Prevents reflux of urine into the uterus

o In VUR, the intravesical portion of the ureter is not

compressed during micturition Urine refluxes into the ureters

ii. Ascending Infection:o Most common mechanism for UTI in females

o Distal urethra and vaginal introitus are normally

colonised by E. Colio Oragnisms ascend into urethra and bladder

Causes urethritis and cystitiso If VUR is present, infected urine ascends to the renal

pelvis and renal parenchyma

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Causes APN

Gross and microscopic findings:i. Greyish white areas of abscess formation are in the cortex +

medullaii. Microabscess formation occurs in the tubular lumens and

intersstitium (Shown below)

Clinical Findings:i. Spiking fever, flank pain

ii. Increased frequency of urinationiii. Painful urination (dysuria)

Laboratory findings:i. WBC casts (key fidning)

ii. Pyuriaiii. Bacteriuria (usually E. Coli)iv. Haematuria

Complications:i. Chronic pyelonephritis

ii. Perinephric abscessiii. Renal Paillary necrosis

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iv. Septicemia with endotoxic shock Chronic Pyelonephritis (CPN)

Pathogensis:i. VUR starting in young girls

ii. Lower urinary tract obstructiono Produces hydronephrosis

o Example:

Prostatic hyperplasia Renal stones

Gross and microscopic findings:i. Reflux type of CPN

o U-shaped cortical scars

overlying a blunt calyxo Visible with

an intravenous pyelogram (IVP)ii. Obstruction type CPN

o Uniform dilation of the calyces

o Diffuse thinning of cortical tissues

iii. Microscopic findingso Chronic inflammation

Secondary scarring of the glomerulio Tubular atrophy

Tubules contain: Eosinophilic material

o Resemble thyroid tissue

‘’Thyroidization’’

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Note here the changes we call "thyroidization." You will see many chronic inflammatory cells in the interstitial tissue and dilated tubules containing pink staining proteinaceous goo, giving the appearance of thyroid colloid. You should note the scarring in the interstitial tissue in general and to some degree around the glomeruli. This is often associated with chronic ischemic injury of the kidney, which worsens as the process proceeds. Think diabetes and hypertension.

Reference: http://medsci.indiana.edu/c602web/602/c602web/renal/slide79.htm

Case 2 - UTI

Clinical and laboratory findingsi. History of recurrent APN

ii. May cause hypertensiono Reflux nephropathy is a cause of hypertension in

childreniii. May cause Chronic Renal Failure (CFR)

Night Sweats:o There is no good evidence based diagnosis answer

Due to the following:i. Limited number of studies on subjects with such ailment

ii. No clinical trial have directly studied symptomatic relief of night sweats alone

iii. History taking is the best initial diagnostic tool ( Strength of recommendation (SOR): C, based on usual practice and clinical opinion)

Very common complaint for:i. Menopausal women with hot flashes

ii. Most common age group in both genders (41-55 years)iii. Common causes not widely studies, mainly attributed to

lymphoma, TUBERCOLOSIS, and HIV infection. o Not common in outpatient care!

iv. Medications, such as:o Antidepressant (SSRIs, Venlafaxine... etc.)

o Antimigranes

o Antipyretics (Aspirin, acetaminophen, and NSAIDS)

o Cholinergic agonists

o GNRH agonists

o Hypoglycaemic agents

o Sympathomimetic agents

o Others, alcohol, beta blockers, and calcium channel

blockers to name a few! Differential diagnosis:

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Tuberculosis (TB)o Epidemiology and pathophysiology:

Contracted by inhalation of Myobacterium tuberculosis Characteristics:

i. Strict aerobe, acid fast (due to mycolic acid in cell wall) Screening:

i. Purified Protein derivative (PPD) intradermal skin testo Does NOT distinguish active from inactive disease

Primary TB:i. Subpleural location

o Upper part of the lower lobes or lower part of the upper

lobesii. Usually resolves

o Produces a calcified granuloma or area of scar tissue

o May be a nidus for secondary TB

Secondary (reactivation) TB:i. Due to reactivation of a previous primary TB site

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ii. Invovles one or both apices in upper lobes of respiratory lungo Ventilation (oxygenation) is greatest in the upper lobes

o Decrease incidence of TB in mountain people

Used to be previous treatment before advent of strong antibiotics

Increased antibiotics resistance M. TB strains brought back mountain less oxygenation regimen

o Cavitary lesion due to release of cytokines from

memory T Cellsiii. Clinical findings:

o Fever

o Drenching night sweats

o Weight loss

iv. Complications:o Miliary spread in lungs due to invasion into the

bronchus or lymphaticso Miliary spread to extrapulmonary sites

Due to invasion of pulmonary vein tributaries Kidney is the most common extrapulmonary site Also called: tuberculosis cutis acuta

generalisatao Massive hemoptysis

o Bronchietctasis

o Scar carcinoma

o Granulomatous hepatitis

o Spread to vertebra (Pott’s disease)

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Referred Pain:o Pain originating in a visceral structure may be referred to and felt in a somatic

structureo Several proposed theories in explaining its mechanism

i. Convergence – projection theory of visceral paino Suggest that two different afferent segments terminate

at the same spinal cord level and end there.o Converging nociceptive inputs into same synaptic

interneuron or second order neurono Transmitted to higher brain centers through the same

dorsal horn and intermediate grey matterii. Concept of referred pain

o Second order GSA are continuously being activated by

GVA first order neuronso Thereby, lowering threshold of stimulation of 2nd order

neuronso Nociceptive inputs is relayed to its somesthetic cortex

o It normally receives normally somatic information from

other areas, such as upper limbo The brain interprets such information as if it was

coming from somewhere elseo Thus, it’s a problem of the terminal end (i.e.,

somatosensory cortex) that interprets the signals not the stimulus or receptor that establish localisation of such sensations

None Proven to be true!!!o Still unknown

o Expanded interest in research after World War II

Due toi. Generalised painful sensations from phantom limb pain of

soldiersii. Increased incidence of myocardial infarcts with the blooming

economic prosperityo Been known as early as 1880’s

o Best example: Angina pectori

i. Pain sensation arising in heart muscleii. Experience as pressure in chest, back , arm

iii. All from regions served by the same segmental spinal nerveo Can be manifested as a toothache, and neck pain

Due to same embryological loci derivation Patients may visit a dentist, but they have

underlying heart problems GO TO A CARDIOLOGIST!!!

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o Other areas (related to the case):

i. Suprapubic pain: Prostate hyperplasiaii. left flank tenderness : pylonephrititis

Urine analysis:o Gold standard in initial work up of kidney function

A diagnostic tooli. Ordered at intervals as a rapid method

o Helps monitor organ’s

Function Status Response to treatment

ii. Commonly ordered due to UTI’s symptomps:o Abdominal pain

o Back pain

o Dysuria, or frequet urination

o Haematuria

iii. Can be useful in monitoring certain conditionso Interpretation of the results:

i. Visual examination:

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o Urine colour, clarity, and concentration

Normal: shades of yellow From very pale to dark amber

o Sometimes blood can contaminate it

Due to haemorroids Woman’s mensturation Other causes (many pathologic)

o Depth of urine:

Crude indicator of its concentration Pale yellow or colourless

Diluted urine (aka, water loss) Dark yellow

Concentrated highly osmotic urineo Seen In first morning urine

o With dehydration

o Or during a fever

o Clarity

Different termss: Clear Slighly cloudy Cloudy Turbid

Normal: clear or cloudy Substances can cause cloudy urine

o Prostatic fluid

o Sperm

o Mucous

o Cells from skin

o Normal urine crystals

Or Bacteria needs attention!!ii. Chemical examination:

o Using prepared test strips

Normal plastic strips holding small squares of test pads paper

They absorb urine once dippped Chemical reactionoccurs Pad colour changes within seconds to

minutes Timing is important in diagnosis

May result in errorso Best use automated instruments

to read

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Change of colour approximated amount of existing substance

Example:o Slight color – small [protein]

o Dark color - large [protein]

o Frequent chemical tests:

Specific Gravity: Indicates urine concentration

o No abnormal values

Comparison between dissoloved substances and water

Test pado Upper limit (1.035)

o Lower limit (1.002)

Underlying causes:o Lack of concentration and

dilution (e.g., CRF)o First sign of intrinsic renal

disease pH:

No abornamal values Indicates acidic or alkaline pH Determined by:

o Diet

- Low carb diet = Alkaline

- High protein diet = Acidico Proteus infection:

Alkaline urine, urease converts urea into ammonia

Can cause crystals due to acidity or alkalinity

o Crystals forming in kidney, are

called ‘’calculus’’ Protein:

Elevated in urine, proteinuriao Early sign of kidney disease

o Normal, little or no protein

Detects albumin (not globulins) SSA: detects albumin and globulins Albuminuria: dipstick and SSA have

same results Disorders that cause it:

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o That can cause high protein level

in bloodo Disorders causes destruction of

RBC’so Inflammation

o Vaginal secretion that get into

urine Glucose:

Not normally present in urine When present, called: glucosuria Results from:

1) Excessive high glucose level in blood, diabetes militus

2) Reduction in renal threshold, normal pregnancy and glucosuria

Ketons: Not normally found in urine

o Intermediate products of fat

metabolism Present in high amounts, called:

ketonuria Can be an early indication of insufficient

insulin

Causes:o Diabetic ketoacidosis

o Starvation

o Ketogenic diets

o Severe exercise

o Exposure to cold

o Carbohydrates loss, (frequent

vomitting) Test only detects acetone and AcAc (not

β-OHB) Blood:

Always pathologic in urine Sometimes chemically can be negative,

but microscopically found positiveo When it happens

We test for ascorbic acid ( vitamin C)

It results into falsely low, or falsely negative

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High levels are called:o Hemoglobinuria

o Hematuria

o Or Myoglobinuria

Underlying causes:o Intravascular haemolytic anaemia

o Renal calculus

o Infection

o Cancer

o Crush injuries

Discussed later in more details, under Haematouria section

Leukocyte esterase: An enzyme present in WBC’s Normally there are few WBC’s in urine

o High levels, will result in this

screening test positive Presence of esterase in neutrophils

(pryuria) Sterile pryuria (neutrophils present but

negative standard urine culture) Underlying causes:

o Infection

o Chlamydia trachomatis urithritis

o Renal tuberclusis

Nitrite: Bacteria convert nitrate into nitrite in

urine When bacteria present, they cause UTI,

leading to increase of nitrites Postive test is an indication of UTI Underlying cause:

o Nitrate reducing uropathogens

ex- E.coli Billirubin:

Not normal present Produced by liver from haemoglobin of

dead circulating RBcs When present, called: Bilirubinuria Underlying cause:

o Viral hepatitis

o Obstructive jaundice

Urobilonogen:

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Present in urine in low concentrationo Derivavitive of bilirubin

Underlying causes:o Obstructive jaundice

o Viral hepatitis

o Extravascular haemolytic anemia

(e.g., spherocytosis)iii. Microscopic examination:

o Cells:

Bacteria Red blood cells (hematuria) Neutrophils (pyuria) Oval fat bodies

Underlying causes:o UTI (commonly)

o Renal stones

o Cancers (bladder, renal)

o Infection

o Benign prostatic hyperplasia

o Sterile pyuria

o Renal tubular cells with lipid

(nephrotic syndrome)

o Casts

Hyaline RBC’s WBC’s Renal tubular cell Fatty Waxy (refactile, acellular)

Haematuriao Definition:

More than three red blood corpuscles are found in centrifuged urine per high power field microscopy (>3RBC/HP).

Aetiology:i. Diseases of urinary system (most common cause)

o Vascular

arteriovenous malformation arterial emboli or thrombosis arteriovenous fistular nutcracker syndrome renal vein thrombosis loin-pain hematuria syndrom

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coagulation abnormality excessive anticoagulation

o Glomerular

IgA nehropathy thin basement membrane disease (Alport

syndrome) other causes of primary and secondary

glomerulonephritiso Interstitial

allergic interstitial nephritis analgesic nephropathy renal cystic diseases acute pyelonephritis tuberculosis renal allograft rejection

o Uroepithelium

malignancy vigorous excise trauma papillary necrosis cystitis/urethritis/prostatitis (usually caused by

infection) parasitic diseases (e.g. schistosomiasis) nephrolithiasis or bladder calculi

o Multiple sites or source unknown

Hypercalciuriaii. System disorders:

o Haematological disorders:

aplastic anemia leukemia allergic purpura hemophilia ITP (idiopathy thrombocytopenic purpura)

o Infection:

infective endocarditis septicemia epidemic hemorrhagic fever (Hantaan virus) scarlet fever (-hemolytic streptococcus) leptospirosis (leptospire) filariasis (Wuchereria bancrofti, Brugia malayi)

o Connective tissue diseases

systemic lupus erythematous (SLE)

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polyarthritis nodosa

o Cardiovascular diseases

hypertensive nephropathy

chronic heart failure

renal artery sclerosis

o Endocrine and metabolism diseases

gout

diabetes mellitus

iii. Diseases of adjacent organs to urinary tracto Appendicitis

o salpingitis

o carcinoma of the rectum

o carcinoma of the colon

o uterocervical cancer

iv. Drug and chemical agents

o Sulfanilamides

o anticoagulation

o cyclophosphamide （CTX)

o mannito

v. miscellaneous

o exercise

o “idopathic” hematuria

Clinical Features:i. Colour:

o Depends on

amount of RBC’s in urine Ph value

Normal:o Yellow colour

o 6.5

ii. pH:o Acidic: more darker (brown or black)

o Alkaline: red

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Red urine, indicative of its alkalinity Dark urine, indicative of its acidity

A) Red cast in urine B) RBC’s in urine

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Drugs:o Fluroquinolones:

1st generation: - Nalidxic acid 2nd generation :

i. Aprofloxicin ii. Norfloxicin

iii. Ofloxoicin 3rd generation: larofloxicin 4th generation: Moxifloxacin Fatal Have broad spectrum activity (gram (+) , and gram (-)) Inhibit DNA replication by interfering with Topoisomerase II, IV Drug of Choice:

o For resistant tuberclusis patient

o Isoniazid:

Prodrug that must be activated by bacterial catalylaseo Enzyme present in M. TB

o Known as kat G.

o Form a complex inhibits fatty acid synthesis

Decreases synthesised mycolic acid No bacterial wall

o Side effects:

Rash

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Hepatitis Anemia Peripheral neuropathy Mild CNS disturbances

o Rifampin:

Inhibit DNA dependant RNA polymeraseo By binding to B-subunit of RNA

o Prevents transcription to RNA

o Thus, no translation to proteins

Side effects:i. Hepatotoxicity (most common)

ii. Respiratory distressiii. Abdominal painiv. Nauseav. Vomitty

vi. Crampsvii. Diarrhoae

viii. Flue-like syndromeo Pyrazinamide:

Prodrug that is a activated by pyrazanmaidase Present in M. Tuberclosis Forms pyrozonic acid Inhibits FAS Distubes bacterial wall

Side effects:i. Most common: arthlagia

ii. Most severe: hepatotoxicityo Ethambatol:

Bacteriostatico Obstruct of cell wall synthesis (TB)

o Disturbs arabinogalactin synthesis

By inhibiting arabynosyl transeferase Important in bacterial

wall synthesisReferences:

o Robbins

o http://medsci.indiana.edu

o Up-to-date

o http://www.edrep.org

o http://acutemed.co.uk

o http://en.diagnosispro.com/

o http://www.nlm.nih.gov

o http://jfponline.com

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